title: Dual role of miR-21 in CD4+ T-cells: activation-induced miR-21 supports survival of memory T-cells and regulates CCR7 expression in naive T-cells.
abstract: Immune cell-type specific miRNA expression patterns have been described but the detailed role of single miRNAs in the function of T-cells remains largely unknown. We investigated the role of miR-21 in the function of primary human CD4+ T-cells. MiR-21 is substantially expressed in T-cells with a memory phenotype, and is robustly upregulated upon αCD3/CD28 activation of both naive and memory T-cells. By inhibiting the endogenous miR-21 function in activated naive and memory T-cells, we showed that miR-21 regulates fundamentally different aspects of T-cell biology, depending on the differentiation status of the T-cell. Stable inhibition of miR-21 function in activated memory T-cells led to growth disadvantage and apoptosis, indicating that the survival of memory T-cells depends on miR-21 function. In contrast, stable inhibition of miR-21 function in activated naive T-cells did not result in growth disadvantage, but led to a significant induction of CCR7 protein expression. Direct interaction between CCR7 and miR-21 was confirmed in a dual luciferase reporter assay. Our data provide evidence for a dual role of miR-21 in CD4+ T cells; Regulation of T-cell survival is confined to activated memory T-cells, while modulation of potential homing properties, through downregulation of CCR7 protein expression, is observed in activated naive T-cells.
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands ; Groningen Research Initiative on healthy Ageing and Immune Longevity (GRAIL), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Smigielska-Czepiel
authors.forename: Anke
authors.initials: A
authors.lastname: van den Berg
authors.forename: Pytrick
authors.initials: P
authors.lastname: Jellema
authors.forename: Izabella
authors.initials: I
authors.lastname: Slezak-Prochazka
authors.forename: Henny
authors.initials: H
authors.lastname: Maat
authors.forename: Hilda
authors.initials: H
authors.lastname: van den Bos
authors.forename: Roelof Jan
authors.initials: RJ
authors.lastname: van der Lei
authors.forename: Joost
authors.initials: J
authors.lastname: Kluiver
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brouwer
authors.forename: Anne Mieke H
authors.initials: AM
authors.lastname: Boots
authors.forename: Bart-Jan
authors.initials: BJ
authors.lastname: Kroesen
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D054400:Receptors, CCR7